This research project will investigate the hypothesis that variation in candidate monoamine-regulatory genes is significantly associated with behavioral and monoaminergic metabolite differences identified between dominant and subordinate cynomolgus macaques, Macaca fascicularis. In addition, this project aims to examine evolutionary changes in these genes through a phylogenetic analysis of sequence variation across representative species from the major primate families. DNA samples are available from approximately 1000 M. fascicularis, for which social rank is known. Cerebrospinal fluid monoamine metabolite concentrations are available for approximately 800 of these individuals. Novel single nucleotide polymorphisms (SNPs) spanning candidate genes of the dopaminergic and serotonergic pathways will be identified. These variants will be examined in all individuals and subjected to haplotype association and linkage disequilibrium analyses to determine if they are associated significantly with social rank and related monoamine metabolite levels. Complete coding and regulatory sequences of these candidate genes will be compared phylogenetically in representatives from major primate families, to assess the extent and direction of evolutionary change of these genes, to identify the ancestral primate genotypes and to date the divergences of each lineage. Little is currently known about the relationship between the genome and complex phenotypic traits such as behavior and neurotransmitter activity. Examining the influence of genetic sequence variation on these phenotypes may help to explain the role the genome plays in determining human behavior patterns, as well as the effects of behavioral selection on evolution of the primate genome. Developing an understanding of these processes in animals such as the nonhuman primates, which display complex social interactions similar to those of humans, may shed light on the evolution of sociality and personality traits such as extraversion, aggression, impulsivity, fear and anxiety in our own species. [unreadable] [unreadable]